For Patients

Taxol (paclitaxel) is a cancer chemotherapy medication that interferes with the growth of cancer cells and slows their growth and spread in the body. Paclitaxel is used to treat breast cancer, lung cancer, and ovarian cancer. It is also used to treat AIDS-related Kaposi's sarcoma. The drug is given through an intravenous infusion administered in a hospital or clinic. Side effects can include increased blood pressure, fever, skin warmth or redness, slow heart rate, and others.

Paclitaxel should not be administered to a pregnant woman. Do not use this medication without telling your doctor if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

Our Taxol Side Effects Drug Center provides a comprehensive vie w of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

This medication may infrequently cause changes to your blood pressure and heart rate. You should be closely monitored for these changes during the infusion of this medication. Tell your doctor promptly if you have increasing dizziness, headache, or a fast/slow/irregular heartbeat.

Many people using this medication have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

This medication may infrequently irritate the vein it is given into or leak out of the vein and irritate the area. These effects may cause redness, pain, swelling, discoloration, or unusual skin reactions at the injection site, either while the drug is given or rarely 7 to 10 days later. If this drug has leaked out of a vein and caused a skin reaction in the past, you may rarely have a skin reaction in that same area when the drug is given again, even when it is given into another area. Tell your doctor immediately of any unusual skin/injection site symptoms.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

SIDE EFFECTS

Data in the following table are based on the experience of 812 patients (493
with ovariancarcinoma and 319 with breast carcinoma) enrolled in 10 studies
who received single- agent TAXOL. Two hundred and seventy-five patients were
treated in 8, Phase 2 studies with TAXOL doses ranging from 135 to 300 mg/m2
administered over 24 hours (in 4 of these studies, G-CSF was administered as
hematopoietic support). Three hundred and one patients were treated in the randomized
Phase 3 ovarian carcinoma study which compared 2 doses (135 or 175 mg/m2)
and 2 schedules (3 or 24 hours) of TAXOL. Two hundred and thirty-six patients
with breast carcinoma received TAXOL (135 or 175 mg/m2) administered
over 3 hours in a controlled study.

a Based on worst course analysis. b All patients received premedication. c During the first 3 hours of infusion. †Severe events are defined as at least Grade III toxicity.

None of the observed toxicities were clearly influenced by age.

Disease-Specific Adverse Event Experiences

First-Line Ovary in Combination: For the 1084 patients who were evaluable
for safety in the Phase 3 first-line ovary combination therapy studies, TABLE
11 shows the incidence of important adverse events. For both studies, the analysis
of safety was based on all courses of therapy (6 courses for the GOG-111 study
and up to 9 courses for the Intergroup study).

Myelosuppression was dose and schedule related, with the schedule effect being more prominent. The development of severe hypersensitivity reactions (HSRs) was rare; 1% of the patients and 0.2% of the courses overall. There was no apparent dose or schedule effect seen for the HSRs. Peripheral neuropathy was clearly dose related, but schedule did not appear to affect the incidence.

Adjuvant Breast: For the Phase 3 adjuvant breast carcinoma study, the
following table shows the incidence of important severe adverse events for the
3121 patients (total population) who were evaluable for safety as well as for
a group of 325 patients (early population) who, per the study protocol, were
monitored more intensively than other patients.

aBased on worst course analysis. bSevere events are defined as at least Grade III toxicity. cPatients received 600 mg/m2 cyclophosphamide and
doxorubicin (AC) at doses of either 60 mg/m2, 75 mg/m2,
or 90 mg/m2 (with prophylactic G-CSF support and ciprofloxacin),
every 3 weeks for 4 courses. dTAXOL (T) following 4 courses of AC at a dose of 175 mg/m2/3
hours every 3 weeks for 4 courses. eThe incidence of febrile neutropenia was not reported in this
study. fAll patients were to receive premedication.

The incidence of an adverse event for the total population likely represents
an underestimation of the actual incidence given that safety data were collected
differently based on enrollment cohort. However, since safety data were collected
consistently across regimens, the safety of the sequential addition of TAXOL
(paclitaxel) following AC therapy may be compared with AC therapy alone. Compared
to patients who received AC alone, patients who received AC followed by TAXOL
experienced more Grade III/IV neurosensory toxicity, more Grade III/IV myalgia/arthralgia,
more Grade III/IV neurologic pain (5% vs 1%), more Grade III/IV flu-like symptoms
(5% vs 3%), and more Grade III/IV hyperglycemia (3% vs 1%). During the additional
4 courses of treatment with TAXOL, 2 deaths (0.1%) were attributed to treatment.
During TAXOL treatment, Grade IV neutropenia was reported for 15% of patients,
Grade II/III neurosensory toxicity for 15%, Grade II/III myalgias for 23%, and
alopecia for 46%.

Breast Cancer After Failure of Initial Chemotherapy: For the 458 patients
who received single-agent TAXOL in the Phase 3 breast carcinoma study, the following
table shows the incidence of important adverse events by treatment arm (each
arm was administered by a 3-hour infusion).

TABLE 14: FREQUENCYa OF IMPORTANT ADVERSE EVENTS
IN THE PHASE 3 STUDY OF BREAST CANCER AFTER FAILURE OF INITIAL CHEMOTHERAPY
OR WITHIN 6 MONTHS OF ADJUVANT CHEMOTHERAPY

Myelosuppression and peripheral neuropathy were dose related. There was one
severe hypersensitivity reaction (HSR) observed at the dose of 135 mg/m2.

First-Line NSCLC in Combination: In the study conducted by the Eastern
Cooperative Oncology Group (ECOG), patients were randomized to either TAXOL
(T) 135 mg/m2 as a 24-hour infusion in combination with cisplatin
(c) 75 mg/m2, TAXOL (T) 250 mg/m2 as a 24-hour infusion
in combination with cisplatin (c) 75 mg/m2 with G-CSF support, or
cisplatin (c) 75 mg/m2 on day 1, followed by etoposide (VP) 100 mg/m2
on days 1, 2, and 3 (control).

The following table shows the incidence of important adverse events.

TABLE 15: FREQUENCYa OF IMPORTANT ADVERSE EVENTS
IN THE PHASE 3 STUDY FOR FIRST-LINE NSCLC

Toxicity was generally more severe in the high-dose TAXOL treatment arm (T250/c75)
than in the low-dose TAXOL arm (T135/c75). Compared to the cisplatin/etoposide
arm, patients in the low-dose TAXOL arm experienced more arthralgia/myalgia
of any grade and more severe neutropenia. The incidence of febrile neutropenia
was not reported in this study.

Kaposi's Sarcoma: The following table shows the frequency of important
adverse events in the 85 patients with KS treated with 2 different single-agent
TAXOL (paclitaxel) regimens.

TABLE 16: FREQUENCYa OF IMPORTANT ADVERSE EVENTS
IN THE AIDS-RELATED KAPOSFS SARCOMA STUDIES

As demonstrated in this table, toxicity was more pronounced in the study utilizing
TAXOL (paclitaxel) at a dose of 135 mg/m2 every 3 weeks than in the study utilizing
TAXOL at a dose of 100 mg/m2 every 2 weeks. Notably, severe neutropenia
(76% vs 35%), febrile neutropenia (55% vs 9%), and opportunistic infections
(76% vs 54%) were more common with the former dose and schedule. The differences
between the 2 studies with respect to dose escalation and use of hematopoietic
growth factors, as described above, should be taken into account. (See Clinical
Studies: AIDS-Related Kaposi's Sarcoma.) Note also that only 26% of the
85 patients in these studies received concomitant treatment with protease inhibitors,
whose effect on paclitaxel metabolism has not yet been studied.

Adverse Event Experiences by Body System

Unless otherwise noted, the following discussion refers to the overall safety
database of 812 patients with solid tumors treated with single-agent TAXOL in
clinical studies. Toxicities that occurred with greater severity or frequency
in previously untreated patients with ovarian carcinoma or NSCLC who received
TAXOL in combination with cisplatin or in patients with breast cancer who received
TAXOL after doxorubicin/cyclophosphamide in the adjuvant setting and that occurred
with a difference that was clinically significant in these populations are also
described. The frequency and severity of important adverse events for the Phase
3 ovarian carcinoma, breast carcinoma, NSCLC, and the Phase 2 Kaposi's sarcoma
studies are presented above in tabular form by treatment arm. In addition, rare
events have been reported from postmarketing experience or from other clinical
studies. The frequency and severity of adverse events have been generally similar
for patients receiving TAXOL for the treatment of ovarian, breast, or lung carcinoma
or Kaposi's sarcoma, but patients with AIDS-related Kaposi's sarcoma may have
more frequent and severe hematologic toxicity, infections (including opportunistic
infections, see TABLE 16), and febrile neutropenia. These patients require
a lower dose intensity and supportive care. (See Clinical Studies: AIDS-Related
Kaposi's Sarcoma.) Toxicities that were observed only in or were noted to
have occurred with greater severity in the population with Kaposi's sarcoma
and that occurred with a difference that was clinically significant in this
population are described. Elevated liver function tests and renal toxicity have
a higher incidence in KS patients as compared to patients with solid tumors.

Hematologic: Bone marrow suppression was the major dose-limiting toxicity
of TAXOL. Neutropenia, the most important hematologic toxicity, was dose and
schedule dependent and was generally rapidly reversible. Among patients treated
in the Phase 3 second-line ovarian study with a 3-hour infusion, neutrophil
counts declined below 500 cells/mm3 in 14% of the patients treated
with a dose of 135 mg/m2 compared to 27% at a dose of 175 mg/m2
(p=0.05). In the same study, severe neutropenia ( < 500 cells/mm3)
was more frequent with the 24-hour than with the 3-hour infusion; infusion duration
had a greater impact on myelosuppression than dose. Neutropenia did not appear
to increase with cumulative exposure and did not appear to be more frequent
nor more severe for patients previously treated with radiation therapy.

In the study where TAXOL was administered to patients with ovarian carcinoma at a dose of 135 mg/m2/24 hours in combination with cisplatin versus the control arm of cyclophosphamide plus cisplatin, the incidences of grade IV neutropenia and of febrile neutropenia were significantly greater in the TAXOL plus cisplatin arm than in the control arm. Grade IV neutropenia occurred in 81% on the TAXOL plus cisplatin arm versus 58% on the cyclophosphamide plus cisplatin arm, and febrile neutropenia occurred in 15% and 4% respectively. On the TAXOL/cisplatin arm, there were 35/1074 (3%) courses with fever in which Grade IV neutropenia was reported at some time during the course. When TAXOL followed by cisplatin was administered to patients with advanced NSCLC in the ECOG study, the incidences of Grade IV neutropenia were 74% (TAXOL 135 mg/m2/24 hours followed by cisplatin) and 65% (TAXOL 250 mg/m2/24 hours followed by cisplatin and G-CSF) compared with 55% in patients who received cisplatin/etoposide.

Fever was frequent (12% of all treatment courses). Infectious episodes occurred
in 30% of all patients and 9% of all courses; these episodes were fatal in 1%
of all patients, and included sepsis, pneumonia and peritonitis. In the Phase
3 second-line ovarian study, infectious episodes were reported in 20% and 26%
of the patients treated with a dose of 135 mg/m2 or 175 mg/m2
given as 3-hour infusions, respectively. Urinary tract infections and upper
respiratory tract infections were the most frequently reported infectious complications.
In the immunosuppressed patient population with advanced HIV disease and poor-risk
AIDS-related Kaposi's sarcoma, 61% of the patients reported at least one opportunistic
infection. (See Clinical Studies: AIDS-Related Kaposi's Sarcoma.) The
use of supportive therapy, including G-CSF, is recommended for patients who
have experienced severe neutropenia. (See DOSAGE AND ADMINISTRATION.)

Thrombocytopenia was reported. Twenty percent of the patients experienced a
drop in their platelet count below 100,000 cells/mm3 at least once while on
treatment; 7% had a platelet count < 50,000 cells/mm3 at the time of their
worst nadir. Bleeding episodes were reported in 4% of all courses and by 14%
of all patients, but most of the hemorrhagic episodes were localized and the
frequency of these events was unrelated to the TAXOL dose and schedule. In the
Phase 3 second-line ovarian study, bleeding episodes were reported in 10% of
the patients; no patients treated with the 3-hour infusion received platelet
transfusions. In the adjuvant breast carcinoma trial, the incidence of severe
thrombocytopenia and platelet transfusions increased with higher doses of doxorubicin.

Anemia (Hb < 11 g/dL) was observed in 78% of all patients and was severe (Hb < 8 g/dL) in 16% of the cases. No consistent relationship between dose or schedule and the frequency of anemia was observed. Among all patients with normal baseline hemoglobin, 69% became anemic on study but only 7% had severe anemia. Red cell transfusions were required in 25% of all patients and in 12% of those with normal baseline hemoglobin levels.

Hypersensitivity Reactions (HSRs): In clinical trials, all patients
received premedication prior to TAXOL administration (see WARNINGS and
PRECAUTIONS: Hypersensitivity Reactions). The frequency and severity
of HSRs were not affected by the dose or schedule of TAXOL administration. In
the Phase 3 second-line ovarian study, the 3-hour infusion was not associated
with a greater increase in HSRs when compared to the 24-hour infusion. Hypersensitivity
reactions were observed in 20% of all courses and in 41% of all patients. These
reactions were severe in less than 2% of the patients and 1% of the courses.
No severe reactions were observed after course 3 and severe symptoms occurred
generally within the first hour of TAXOL infusion. The most frequent symptoms
observed during these severe reactions were dyspnea, flushing, chest pain, and
tachycardia. Abdominal pain, pain in the extremities, diaphoresis, and hypertension
were also noted.

Chills, shock, and back pain in association with hypersensitivity reactions have been reported.

Cardiovascular: Hypotension, during the first 3 hours of infusion, occurred
in 12% of all patients and 3% of all courses administered. Bradycardia, during
the first 3 hours of infusion, occurred in 3% of all patients and 1% of all
courses. In the Phase 3 second-line ovarian study, neither dose nor schedule
had an effect on the frequency of hypotension and bradycardia. These vital sign
changes most often caused no symptoms and required neither specific therapy
nor treatment discontinuation. The frequency of hypotension and bradycardia
were not influenced by prior anthracycline therapy.

Significant cardiovascular events possibly related to single-agent TAXOL (paclitaxel) occurred in approximately 1% of all patients. These events included syncope, rhythm abnormalities, hypertension, and venous thrombosis. One of the patients with syncope treated with TAXOL at 175 mg/m2 over 24 hours had progressive hypotension and died. The arrhythmias included asymptomaticventricular tachycardia, bigeminy, and complete AV block requiring pacemaker placement. Among patients with NSCLC treated with TAXOL in combination with cisplatin in the Phase 3 study, significant cardiovascular events occurred in 12 to 13%. This apparent increase in cardiovascular events is possibly due to an increase in cardiovascular risk factors in patients with lung cancer.

Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 23% of all patients. Among patients with a normal ECG prior to study entry, 14% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, sinus tachycardia, and premature beats. Among patients with normal ECGs at baseline, prior therapy with anthracyclines did not influence the frequency of ECG abnormalities.

Neurologic: The assessment of neurologic toxicity was conducted differently
among the studies as evident from the data reported in each individual study
(see TABLES 10-16). Moreover, the frequency and severity of neurologic
manifestations were influenced by prior and/or concomitant therapy with neurotoxic
agents.

In general, the frequency and severity of neurologic manifestations were dose-dependent
in patients receiving single-agent TAXOL. Peripheral neuropathy was observed
in 60% of all patients (3% severe) and in 52% (2% severe) of the patients without
pre-existing neuropathy. The frequency of peripheral neuropathy increased with
cumulative dose. Paresthesia commonly occurs in the form of hyperesthesia. Neurologic
symptoms were observed in 27% of the patients after the first course of treatment
and in 34 to 51% from course 2 to 10. Peripheral neuropathy was the cause of
TAXOL discontinuation in 1% of all patients. Sensory symptoms have usually improved
or resolved within several months of TAXOL discontinuation. Pre-existing neuropathies
resulting from prior therapies are not a contraindication for TAXOL therapy.

In the Intergroup first-line ovarian carcinoma study (see TABLE 11),
neurotoxicity included reports of neuromotor and neurosensory events. The regimen
with TAXOL 175 mg/m2 given by 3-hour infusion plus cisplatin 75 mg/m2
resulted in greater incidence and severity of neurotoxicity than the regimen
containing cyclophosphamide and cisplatin, 87% (21% severe) versus 52% (2% severe),
respectively. The duration of grade III or IV neurotoxicity cannot be determined
with precision for the Intergroup study since the resolution dates of adverse
events were not collected in the case report forms for this trial and complete
follow-up documentation was available only in a minority of these patients.
In the GOG first-line ovarian carcinoma study, neurotoxicity was reported as
peripheral neuropathy. The regimen with TAXOL 135 mg/m2 given by
24-hour infusion plus cisplatin 75 mg/m2 resulted in an incidence
of neurotoxicity that was similar to the regimen containing cyclophosphamide
plus cisplatin, 25% (3% severe) versus 20% (0% severe), respectively. Cross-study
comparison of neurotoxicity in the Intergroup and GOG trials suggests that when
TAXOL is given in combination with cisplatin 75 mg/m2, the incidence
of severe neurotoxicity is more common at a TAXOL dose of 175 mg/m2
given by 3-hour infusion (21%) than at a dose of 135 mg/m2 given
by 24-hour infusion (3%).

In patients with NSCLC, administration of TAXOL followed by cisplatin resulted
in a greater incidence of severe neurotoxicity compared to the incidence in
patients with ovarian or breast cancer treated with single-agent TAXOL. Severe
neurosensory symptoms were noted in 13% of NSCLC patients receiving TAXOL 135
mg/m2 by 24-hour infusion followed by cisplatin 75 mg/m2 and 8% of
NSCLC patients receiving cisplatin/etoposide (see TABLE 15).

Other than peripheral neuropathy, serious neurologic events following TAXOL administration have been rare ( < 1%) and have included grand mal seizures, syncope, ataxia, and neuroencephalopathy.

Autonomic neuropathy resulting in paralytic ileus has been reported. Optic nerve and/or visual disturbances (scintillating scotomata) have also been reported, particularly in patients who have received higher doses than those recommended. These effects generally have been reversible. However, reports in the literature of abnormal visual evoked potentials in patients have suggested persistent optic nerve damage. Postmarketing reports of ototoxicity (hearing loss and tinnitus) have also been received.

Convulsions, dizziness, and headache have been reported.

Arthralgia/Myalgia: There was no consistent relationship between dose
or schedule of TAXOL and the frequency or severity of arthralgia/myalgia. Sixty
percent of all patients treated experienced arthralgia/myalgia; 8% experienced
severe symptoms. The symptoms were usually transient, occurred 2 or 3 days after
TAXOL administration, and resolved within a few days. The frequency and severity
of musculoskeletal symptoms remained unchanged throughout the treatment period.

Hepatic: No relationship was observed between liver function abnormalities
and either dose or schedule of TAXOL administration. Among patients with normal
baseline liver function 7%, 22%, and 19% had elevations in bilirubin, alkaline
phosphatase, and AST (SGOT), respectively. Prolonged exposure to TAXOL was not
associated with cumulative hepatic toxicity.

Renal: Among the patients treated for Kaposi's sarcoma with TAXOL, 5 patients had renal toxicity of grade III or IV severity. One patient with suspected HIV nephropathy of grade IV severity had to discontinue therapy. The other 4 patients had renal insufficiency with reversible elevations of serum creatinine.

Patients with gynecological cancers treated with TAXOL and cisplatin may have an increased risk of renal failure with the combination therapy of paclitaxel and cisplatin in gynecological cancers as compared to cisplatin alone.

Gastrointestinal (GI): Nausea/vomiting, diarrhea, and mucositis were
reported by 52%, 38%, and 31% of all patients, respectively. These manifestations
were usually mild to moderate. Mucositis was schedule dependent and occurred
more frequently with the 24-hour than with the 3-hour infusion.

In patients with poor-risk AIDS-related Kaposi's sarcoma, nausea/vomiting, diarrhea, and mucositis were reported by 69%, 79%, and 28% of patients, respectively. One-third of

In the first-line Phase 3 ovarian carcinoma studies, the incidence of nausea and vomiting when TAXOL was administered in combination with cisplatin appeared to be greater compared with the database for single-agent TAXOL in ovarian and breast carcinoma. In addition, diarrhea of any grade was reported more frequently compared to the control arm, but there was no difference for severe diarrhea in these studies.

Intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, dehydration, esophagitis, constipation, and ascites have been reported. Neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, was observed in patients treated with TAXOL alone and in combination with other chemotherapeutic agents.

Injection Site Reaction: Injection site reactions, including reactions
secondary to extravasation, were usually mild and consisted of erythema, tenderness,
skin discoloration, or swelling at the injection site. These reactions have
been observed more frequently with the 24-hour infusion than with the 3-hour
infusion. Recurrence of skin reactions at a site of previous extravasation following
administration of TAXOL at a different site, ie, "recall," has been
reported.

More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been reported. In some cases the onset of the injection site reaction either occurred during a prolonged infusion or was delayed by a week to 10 days.

A specific treatment for extravasation reactions is unknown at this time. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.

Other Clinical Events: Alopecia was observed in almost all (87%) of
the patients. Transient skin changes due to TAXOL-related hypersensitivity reactions
have been observed, but no other skin toxicities were significantly associated
with TAXOL administration. Nail changes (changes in pigmentation or discoloration
of nail bed) were uncommon (2%). Edema was reported in 21% of all patients (17%
of those without baseline edema); only 1% had severe edema and none of these
patients required treatment discontinuation. Edema was most commonly focal and
disease-related. Edema was observed in 5% of all courses for patients with normal
baseline and did not increase with time on study.

Skin abnormalities related to radiation recall as well as maculopapular rash, pruritus, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. In postmarketing experience, diffuse edema, thickening, and sclerosing of the skin have been reported following TAXOL administration. TAXOL has been reported to exacerbate signs and symptoms of scleroderma.

Reports of asthenia and malaise have been received as part of the continuing surveillance of TAXOL safety. In the Phase 3 trial of TAXOL 135 mg/m2 over 24 hours in combination with cisplatin as first-line therapy of ovarian cancer, asthenia was reported in 17% of the patients, significantly greater than the 10% incidence observed in the control arm of cyclophosphamide/cisplatin.